Effect of growth hormone on rat hepatic cytochrome P-450f mRNA: a new mode of regulation.
Growth hormone (GH) is known to be involved in the control of rat hepatic drug and steroid metabolism through its action on cytochrome P-450s. To examine the role of GH in the regulation of cytochrome P-450f (P-450f), a full-length cDNA clone corresponding to P-450f was isolated and the 3'-non-coding region was utilized for Northern and slot-blot analyses. P-450f mRNA levels were low in neonates, increased after age 4 weeks in male and female rats, and were approximately 3 times higher in the liver of adult female rats than male rats. Hypophysectomy caused a significant decrease in P-450f mRNA levels in male and female rats. Intermittent injection with human growth hormone (hGH) to mimic the male secretory pattern of GH caused a 9-fold increase in P-450f mRNA in hypophysectomized male rats to levels near male control levels, whereas continuous administration of hGH to mimic the female secretory pattern caused a greater increase in P-450f mRNA levels in male and female hypophysectomized rats (25-fold and 9-fold respectively) to levels nearer female control levels. The responses of the other GH-stimulated P-450s, P-450-male and P-450-female, to the different modes of hGH treatment were different from that of P-450f. Since sex hormones are known to affect the regulation of other P-450s, the effect of sex hormones on P-450f mRNA was studied. Ovariectomy caused a 2.4-fold reduction in P-450f mRNA which was partially reversed by estradiol treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Sasamura
H
H
Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.
Nagata
K
K
Yamazoe
Y
Y
Shimada
M
M
Saruta
T
T
Kato
R
R
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006062:Gonadotropins / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D006062:Gonadotropins; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System